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出境医 / 临床实验 / CAR-T Cell Therapy Targeting to CD19 for R/R ALL

CAR-T Cell Therapy Targeting to CD19 for R/R ALL

Study Description
Brief Summary:
Refractory and relapsed (R/R) acute lymphoblastic leukemia (ALL) patients with active disease always have a dismal outcome. Chimeric antigen receptor (CAR) T-cell therapy targeting to Cluster of Differentiation Antigen 19 (CD19) has been proved as a potent approach to attain remission in B-cell R/R patients. Therefore, the investigators conduct a trial to evaluate the the efficacy and safety of locally producing CAR T cells targeting CD19, and to analyze the outcome of enrolled B-cell ALL patients with active disease or persistent residual disease.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia With Failed Remission Biological: CAR T-cell therapy Phase 1 Phase 2

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CD19-targeting Chimeric Antigen Receptor T-cell Therapy for Patients With Refractory and Relapsed B-cell Acute Lymphoblastic Leukemia
Actual Study Start Date : December 1, 2015
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: CAR T-cell therapy
Patients enrolled will receive infusion of CD19-targeting CAR T-cells
 Biological: CAR T-cell therapy
Patients enrolled will receive infusion of CD19-targeting CAR T-cells with a target dose of 5~10×10E6/kg of recipient weight, after the preparative regimen consisted of fludarabin (30mg/m2, day -5 to -3) and cyclophosphamide (300mg/m2, day -5 to -3).
Outcome Measures
Primary Outcome Measures :
  1. Complete remission [ Time Frame: 1 month post infusion ]
    defined as less than 5% blasts in the bone marrow without myelosuppression, no circulating blasts in peripheral blood, and the absence of extramedullary disease, regardless of cell count recovery

  2. Minimal residual disease response [ Time Frame: 1 month post infusion ]
    defined as less than 0.01% bone marrow blasts assessed by multiparameter flow cytometry, and absence of genetic aberrants assessed by karyotype analysis or molecular detection

  3. Cytokine release syndrome [ Time Frame: 1 month post infusion ]
    grading according to the criteria proposed by Lee, et al (Blood, 2014, 124: 188-195). This grading system ranges from grade 1 (best) to grade 5 (worst), by measuring related symptoms (such as fever, nausea, fatigue, headache, etc.), oxygen requirement, blood pressure and organ toxicity (referred to CTCAE v4.0 grading)


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 1 year post infusion ]
    calculating from the day of CAR T-cell infusion to death or the end of follow-up

  2. Leukemia-free survival [ Time Frame: 1 year post infusion ]
    calculating from the day of CAR T-cell infusion to death, disease progression or the end of follow-up

  3. Cumulative incidence of relapse [ Time Frame: 1 year post infusion ]
    calculating from the day of CAR T-cell infusion to disease progression or the end of follow-up


Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed as CD19+ B-cell acute lymphoblastic leukemia;
  • Fail to achieve remission, or with persistent residual disease after at least 2 cycles of consolidation;
  • With an estimated survival of higher than 3 months (according to investigator's judgement);
  • Sufficient organ function: left ventricular ejection fractions≥ 0.5 by echocardiography, creatinine < 1.6 mg/dL, aspartate aminotransferase/aspartate aminotransferase < 3 x upper limit of normal, bilirubin <2.0 mg/dL;
  • Karnofsky performance status ≥ 60 or ECOG ≤ 2.

Exclusion Criteria:

  • Intolerant to immunosuppressive chemotherapies;
  • With active infection or other uncontrolled complications;
  • With history of seizure;
  • Active hepatitis B or hepatitis C infection and HIV infection;
  • Pregnant or lactating women, or patients refusing to take effective contraception measures;
  • Other contraindications that considered inappropriate to participate in this trial (according to investigator's judgement).
Contacts and Locations

Contacts
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Contact: Jia Chen, M.D., Ph.D. +86 512 67781856 drchenjia@163.com
Contact: Xiang Zhang, M.D. +86 512 67781856 lcsy2013@sina.com

Locations
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China, Jiangsu
The Fisrt Affiliated Hospital of Soochow University Recruiting
Suzhou, Jiangsu, China, 215006
Contact: Depei Wu, M.D., Ph.D.    +86 512 6778 1856    wudepei@medmail.com.cn   
Contact: Jia Chen, M.D.    +86 512 6778 1856    chenjia@suda.edu.cn   
Principal Investigator: Depei Wu, M.D., Ph.D.         
Sub-Investigator: Jia Chen, M.D.         
Sub-Investigator: Aining Sun, M.D., Ph.D.         
Sub-Investigator: Huiying Qiu, M.D., Ph.D.         
Sub-Investigator: Xiaowen Tang, M.D., Ph.D.         
Sub-Investigator: Yue Han, M.D., Ph.D.         
Sub-Investigator: Zhengming Jin, M.D.         
Sub-Investigator: Chengcheng Fu, M.D., Ph.D.         
Sub-Investigator: Feng Chen, M.D., Ph.D.         
Sub-Investigator: Xiao Ma, M.D., Ph.D.         
Sub-Investigator: Suning Chen, M.D., Ph.D.         
Sub-Investigator: Xiang Zhang, M.D.         
Sponsors and Collaborators
The First Affiliated Hospital of Soochow University
Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
Investigators
Layout table for investigator information
Principal Investigator: Depei Wu, M.D., Ph.D. The First Affiliated Hospital of Soochow University
Tracking Information
First Submitted Date  ICMJE April 15, 2019
First Posted Date  ICMJE April 18, 2019
Last Update Posted Date July 1, 2020
Actual Study Start Date  ICMJE December 1, 2015
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2019)
  • Complete remission [ Time Frame: 1 month post infusion ]
    defined as less than 5% blasts in the bone marrow without myelosuppression, no circulating blasts in peripheral blood, and the absence of extramedullary disease, regardless of cell count recovery
  • Minimal residual disease response [ Time Frame: 1 month post infusion ]
    defined as less than 0.01% bone marrow blasts assessed by multiparameter flow cytometry, and absence of genetic aberrants assessed by karyotype analysis or molecular detection
  • Cytokine release syndrome [ Time Frame: 1 month post infusion ]
    grading according to the criteria proposed by Lee, et al (Blood, 2014, 124: 188-195). This grading system ranges from grade 1 (best) to grade 5 (worst), by measuring related symptoms (such as fever, nausea, fatigue, headache, etc.), oxygen requirement, blood pressure and organ toxicity (referred to CTCAE v4.0 grading)
Original Primary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
  • Complete remission [ Time Frame: 1 month post infusion ]
    defined as less than 5% blasts in the bone marrow without myelosuppression, no circulating blasts in peripheral blood, and the absence of extramedullary disease, regardless of cell count recovery
  • Minimal residual disease response [ Time Frame: 1 month post infusion ]
    defined as less than 0.01% bone marrow blasts assessed by multiparameter flow cytometry, and absence of genetic aberrants assessed by karyotype analysis or molecular detection
  • Cytokine release syndrome [ Time Frame: 1 month post infusion ]
    grading according to the criteria proposed by Lee, et al (Blood, 2014, 124: 188-195)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 15, 2019)
  • Overall survival [ Time Frame: 1 year post infusion ]
    calculating from the day of CAR T-cell infusion to death or the end of follow-up
  • Leukemia-free survival [ Time Frame: 1 year post infusion ]
    calculating from the day of CAR T-cell infusion to death, disease progression or the end of follow-up
  • Cumulative incidence of relapse [ Time Frame: 1 year post infusion ]
    calculating from the day of CAR T-cell infusion to disease progression or the end of follow-up
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CAR-T Cell Therapy Targeting to CD19 for R/R ALL
Official Title  ICMJE CD19-targeting Chimeric Antigen Receptor T-cell Therapy for Patients With Refractory and Relapsed B-cell Acute Lymphoblastic Leukemia
Brief Summary Refractory and relapsed (R/R) acute lymphoblastic leukemia (ALL) patients with active disease always have a dismal outcome. Chimeric antigen receptor (CAR) T-cell therapy targeting to Cluster of Differentiation Antigen 19 (CD19) has been proved as a potent approach to attain remission in B-cell R/R patients. Therefore, the investigators conduct a trial to evaluate the the efficacy and safety of locally producing CAR T cells targeting CD19, and to analyze the outcome of enrolled B-cell ALL patients with active disease or persistent residual disease.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Lymphoblastic Leukemia With Failed Remission
Intervention  ICMJE Biological: CAR T-cell therapy
Patients enrolled will receive infusion of CD19-targeting CAR T-cells with a target dose of 5~10×10E6/kg of recipient weight, after the preparative regimen consisted of fludarabin (30mg/m2, day -5 to -3) and cyclophosphamide (300mg/m2, day -5 to -3).
Study Arms  ICMJE Experimental: CAR T-cell therapy
Patients enrolled will receive infusion of CD19-targeting CAR T-cells
Intervention: Biological: CAR T-cell therapy
Publications *
  • Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, Grupp SA, Mackall CL. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 Jul 10;124(2):188-95. doi: 10.1182/blood-2014-05-552729. Epub 2014 May 29. Erratum in: Blood. 2015 Aug 20;126(8):1048. Dosage error in article text. Blood. 2016 Sep 15;128(11):1533.
  • Liu ZF, Chen LY, Wang J, Kang LQ, Tang H, Zhou Y, Zhou HX, Sun AN, Wu DP, Xue SL. Successful treatment of acute B lymphoblastic leukemia relapse in the skin and testicle by anti-CD19 CAR-T with IL-6 knocking down: a case report. Biomark Res. 2020 May 6;8:12. doi: 10.1186/s40364-020-00193-5. eCollection 2020.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 15, 2019) 		50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosed as CD19+ B-cell acute lymphoblastic leukemia;
  • Fail to achieve remission, or with persistent residual disease after at least 2 cycles of consolidation;
  • With an estimated survival of higher than 3 months (according to investigator's judgement);
  • Sufficient organ function: left ventricular ejection fractions≥ 0.5 by echocardiography, creatinine < 1.6 mg/dL, aspartate aminotransferase/aspartate aminotransferase < 3 x upper limit of normal, bilirubin <2.0 mg/dL;
  • Karnofsky performance status ≥ 60 or ECOG ≤ 2.

Exclusion Criteria:

  • Intolerant to immunosuppressive chemotherapies;
  • With active infection or other uncontrolled complications;
  • With history of seizure;
  • Active hepatitis B or hepatitis C infection and HIV infection;
  • Pregnant or lactating women, or patients refusing to take effective contraception measures;
  • Other contraindications that considered inappropriate to participate in this trial (according to investigator's judgement).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jia Chen, M.D., Ph.D. +86 512 67781856 drchenjia@163.com
Contact: Xiang Zhang, M.D. +86 512 67781856 lcsy2013@sina.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03919240
Other Study ID Numbers  ICMJE SZ4601
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The First Affiliated Hospital of Soochow University
Study Sponsor  ICMJE The First Affiliated Hospital of Soochow University
Collaborators  ICMJE Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
Investigators  ICMJE
Principal Investigator: Depei Wu, M.D., Ph.D. The First Affiliated Hospital of Soochow University
PRS Account The First Affiliated Hospital of Soochow University
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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